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Differential influence of additives on the various stages of insulin aggregation

机译:添加剂对胰岛素聚集各个阶段的差异影响

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摘要

The kinetics of aggregation of insulin at pH 1.6 was studied by monitoring the turbidity as a function of time. The aggregation of insulin occurs by a typical nucleation-growth mechanism, resulting in a distinct lag phase, followed by a growth phase and a saturation phase. Sugars and polyols affect the lag time and the rate constant of growth to different extents, suggesting that these additives affect both the pre-and post-nucleation processes. Sucrose and ethylene glycol effectively reduce the aggregation, whereas mannitol is not effective in suppressing the overall aggregation. However, it can delay the aggregation process. It is also inferred that nucleation and elongation may not be affected in the same manner in the presence of a particular additive. The varying behaviour of different additives suggests their interference in the different stages of aggregation, affecting the aggregation intermediates differently. The viscosity of the medium has a minimal effect on the nucleation process, but does affect the elongation rate. The temperature dependence of the aggregation profiles provides probable reasons for the inhibitory action of these additives. The results also suggest the existence of different types of interactions between the additives and the various species in the aggregation pathway of insulin.
机译:通过将浊度作为时间的函数监测浊度来研究pH 1.6在pH 1.6的聚集动力学。胰岛素的聚集通过典型的成核 - 生长机制发生,导致明显的滞后阶段,其次是生长阶段和饱和相。糖和多元醇影响滞后时间和生长的速率常数对不同的范围,这表明这些添加剂影响了预先和后后的过程。蔗糖和乙二醇有效地减少了聚集体,而甘露醇在抑制整体聚集方面无效。但是,它可以延迟聚合过程。还推断,在特定添加剂存在下,成核和伸长率可能不会以相同的方式影响。不同添加剂的不同行为表明它们在聚集的不同阶段的干扰,不同地影响聚集中间体。培养基的粘度对成核过程具有最小的影响,但确实影响了伸长率。聚集型材的温度依赖性提供了这些添加剂的抑制作用的可能原因。结果还表明,添加剂和胰岛素聚集途径中添加剂和各种物种之间存在不同类型的相互作用。

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  • 来源
    《RSC Advances》 |2016年第34期|共13页
  • 作者单位

    Indian Inst Technol Dept Chem Hauz Khas Delhi 110016 India;

    Indian Inst Technol Dept Chem Hauz Khas Delhi 110016 India;

    Indian Inst Technol Dept Chem Hauz Khas Delhi 110016 India;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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